Abstract

Preconditioning has only been demonstrated in arterially perfused myocardium. Our aim was to develop a model of preconditioning in isolated, superfused, isometrically contracting rabbit right ventricular papillary muscle. This would eventually allow us to evaluate isolated human muscles. Papillary muscles were suspended in an organ bath, superfused with oxygenated Tyrode solution, and field stimulated at 1 Hz. Muscles were assigned either to control or to preconditioning groups. Preconditioning was induced with 3 min of rapid pacing (3 Hz) with substrate-free hypoxic buffer and was followed by 15 min of reoxygenation with substrate. Subsequently, both groups were exposed to 45 min of substrate-free hypoxia followed by 120 min of reoxygenation with substrate. Preconditioning protected the myocardium with better recovery of developed force (50.6 +/- 6.7 vs. 27.4 +/- 4.2% of baseline developed force, P < 0.01). This effect could be blocked by 8-(p-sulfophenyl)theophylline (SPT) given during preconditioning at a dose that did not increase hypoxic damage in controls (percent developed force compared to baseline: preconditioned muscles + SPT = 30.9 +/- 2.8% and control muscles + SPT = 27.1 +/- 2.3%). In addition, pretreatment with (-)N-6(2-phenylisopropyl)adenosine similarly protected the myocardium (49.5 +/- 5.5% recovery, P < 0.01). We conclude that isolated superfused muscles can be preconditioned. This preconditioning does not depend on coronary flow and involves activation of adenosine receptors.